NON-INVASIVE SCREENING TEST PARADOX IN A CASE BORN WITH MIXED GONADAL DYSGENESIS (45,X/46,XY)
Cobanogullari H., Akcan N., Ergoren M.C.
*Corresponding Author: Assoc. Prof. M.C. Ergoren, PhD, Near East University, Faculty of Medicine, Department
of Medical Genetics, 99138 Nicosia, Cyprus. E-mail address: mahmutcerkez.ergoren@neu.edu.tr
page: 57
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INTRODUCTION
Turner syndrome (TS) is a chromosomal disorder
commonly observed in females and caused by structural
or numerical abnormalities of the X chromosome. TS affects
1 in 2500 live births [1]. Patients diagnosed with
Turner syndrome have a unique phenotype that includes
a webbed neck, broad chest, and low posterior hairline. In
addition, structural cardiac abnormalities, gonadal dysgenesis,
hypertension and diabetes are some of the secondary
sex characteristics observed in patients with Turner syndrome
[2,3]. Nearly 40-60% of TS patients have a 45,X
karyotype, on the other hand, 45,X/46, XX; 46,X,i(Xq);
and other variants are observed in several TS patients [1].
The gene responsible from short stature is found in the
pseudoautosomal region 1 (PAR1), which is located on
the short arm of the X chromosome and it is defined as
the short stature homeobox-containing (SHOX) gene [4].
Furthermore, mixed gonadal dysgenesis can be
observed in females with Turner syndrome who have
45,X/46,XY mosaicism or sex-determining region Y (SRY)
gene [5]. The presence of a whole Y chromosome or Yderived
material is observed in a range of 4% to 61% in
TS patients with different karyotypes [6]. Mixed gonadal
dysgenesis (MGD) comprises a heterogeneous group of
different chromosomal, gonadal, and phenotypic abnormalities
characterized by the presence of a testis on one
side and a contralateral stripe or absent gonad. Therefore,
the phenotype varies from normal male patients to patients
with ambiguous external genitalia to female patients [7,8].
Cytogenetic analysis is routinely performed for the
genetic diagnosis of Turner syndrome. However, in recent
years, molecular techniques such as polymerase chain
reaction and single nucleotide polymorphism (SNP) genotyping
have been used to detect sex chromosome abnormalities
in a very short time with a low cost, using
both blood and buccal samples. Especially with the recent
improvements in technology, array comparative genomic
hybridization (acGH) has been used to understand the
genetic basis of Turner Syndrome [1].
Cell-free-non-invasive prenatal testing (cfNIPT) has
been widely used as a screening for fetal trisomy 13, 18,
and 21, and it is also used for the screening of sex chromosomal
aneuploidies (SCAs) by analyzing cell-free fetal
DNA (cffDNA) in maternal plasma [7,9]. In addition,
improvements in molecular genomics enabled the use of
NIPT to screen for copy number variants (CNVs) and
various single gene disorders [10]. It has been shown that
cfNIPT is highly sensitive and specific for trisomiy 21
(sensitivity: >99%), trisomy 13 (sensitivity: >98%), and
trisomy 18 (sensitivity: >99%) [7]. However, the concurrence
is lower for SCAs (from 90.5 to 100%). Moreover,
the positive predictive value (PPV) for sex chromosomal
anomalies is lower than for common trisomies, ranging
from 9% to 40% [4,11].
The mosaic Turner Syndrome may be under-diagnosed
due to several reasons, such as subtle phenotypic
characteristics and technical problems [12]. This is mainly
observed in patients who have low rates of mosaicism
due to an increased number of euploid cells or may be
described as an artifact that may affect the true genetic
diagnosis of Turner Syndrome [1].
In the literature, it has been emphasized that low
levels of fetus-driven cell-free DNA concentration in the
blood is one of the limitations of NIPT while detecting
sex chromosomal anomalies. More importantly, the performance
of NIPT in detecting mosaicism has not been
adequately studied. In this report, we present a case in
which the NIPT diagnosis was originally 45,X and the
patient was diagnosed with mixed gonadal dysgenesis
45,X /46,XY after birth.
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